Varano Flavia, Catarzi Daniela, Colotta Vittoria, Lenzi Ombretta, Filacchioni Guido, Galli Alessandro, Costagli Chiara
Dipartimento di Scienze Farmaceutiche, Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi, Università degli Studi di Firenze, Polo Scientifico, via Ugo Schiff, 6, 50019 Sesto Fiorentino (FI), Italy.
Bioorg Med Chem. 2008 Mar 1;16(5):2617-26. doi: 10.1016/j.bmc.2007.11.046. Epub 2007 Nov 22.
This paper reports the synthesis and AMPA, Gly/NMDA, and KA receptor binding affinities of a new set of 1,9-disubstituted-8-chloro-pyrazolo[1,5-c]quinazoline-2-carboxylates 2-34. Binding data show that, in general, compounds 2-34 bind to the AMPA receptor with good affinity and selectivity. In particular, the obtained results indicate that the contemporary presence of a 1,2-dicarboxylic acid moiety and suitable benzo-substituents on the PQZ system is important to gain selective AMPA receptor antagonists. Moreover, this study shows that the presence of a 2-carboxybenzoylamino substituent at position-9 (compounds 33-34) is important for obtaining selective KA receptor antagonists. Some selected compounds were also tested for their functional antagonistic activity at both AMPA and NMDA receptor-ion channels.
本文报道了一组新的1,9-二取代-8-氯-吡唑并[1,5-c]喹唑啉-2-羧酸酯2-34的合成及其对AMPA、甘氨酸/NMDA和KA受体的结合亲和力。结合数据表明，一般来说，化合物2-34对AMPA受体具有良好的亲和力和选择性。特别地，所获得的结果表明，PQZ体系上同时存在1,2-二羧酸部分和合适的苯取代基对于获得选择性AMPA受体拮抗剂很重要。此外，本研究表明，9位存在2-羧基苯甲酰胺基取代基（化合物33-34）对于获得选择性KA受体拮抗剂很重要。还测试了一些选定化合物对AMPA和NMDA受体离子通道的功能拮抗活性。
